title: Encryption and decryption of tissue factor.
abstract: Tissue factor (TF) is a transmembrane cofactor that binds and promotes the catalytic activity of factor (F) VIIa. The TF/VIIa complex activates FX by limited proteolysis to initiate blood coagulation and helps provide the thrombin burst that is important for a stable thrombus. TF is present both in the extravascular compartment, where it functions as a hemostatic envelope, and the intravascular compartment, where it contributes to thrombus formation, particularly when endothelial disruption is minimal. The regulation of its cofactor function appears to differ in the two compartments. Intravascular TF derives predominately from leucocytes, with either monocytes or neutrophils implicated in different models of thrombosis. This TF exists mostly in a non-coagulant or cryptic form and acute events lead to local decryption of TF and FX activation. A variety of experimental observations imply that decryption of leucocyte surface TF involves both a dithiol/disulfide switch and exposure of phosphatidylserine. The dithiol/disulfide switch appears to involve the Cys186-Cys209 disulfide bond in the membrane-proximal domain of TF, although this has not been demonstrated in vivo. Activation of a purinergic receptor or complement has recently been observed to decrypt TF on myeloid cells and a dithiol/disulfide switch and the oxidoreductase, protein disulfide isomerase, have been implicated in both systems. The molecular mechanism of action of protein disulfide isomerase in TF encryption/decryption, though, remains to be determined.
authors.affiliation: Lowy Cancer Research Centre and Prince of Wales Clinical School, University of New South Wales, Sydney, NSW, Australia.
authors.forename: V M
authors.initials: VM
authors.lastname: Chen
authors.forename: P J
authors.initials: PJ
authors.lastname: Hogg
mesh_terms: D001777:Blood Coagulation; D006801:Humans; D013925:Thromboplastin / Q000378:metabolism*
chemical_list: D013925:Thromboplastin
keywords: allosteric disulfide bond; coagulation; decryption; encryption; thrombosis; tissue factor